PONE-D-21-21807Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeriesPLOS ONE

Dear Dr. Caramelli,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please, carefully address all comments and suggestions  and return a revised  version at your earlier convenience.

Please submit your revised manuscript by Nov 04 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Cesario Bianchi

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 

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3. Thank you for stating the following in the Competing Interests section: 

I have read the journal's policy and the authors of this manuscript have the following competing interests: Thiago Artioli received grant from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 2019/17036-4]. Dr. Gualandro received grant from FAPESP and consulting fees from Roche, outside the submitted work. Dr. Francisco Akira Malta Cardozo received honoraria for lectures from Bayer. Dr. Calderaro received payment for lectures from Bayer, Daiichi Sankyo and Janssen; support for attending international meetings: Bayer and Daiichi Sankyo; participation on data safety monitoring board: Bayer. Dr. Ivan Benaduce Casella received consulting fees and honoraria for lectures from Bayer, Daiichi Sankyo and Boehringer Ingelheim. Dr. Bruno Caramelli received an unrestricted grant from the National Council for Scientific and Technological Development – CNPQ [grant number 304352/2016-0].

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Additional Editor Comments:

Dear Dr. Caramelli;

Your manuscript was reviewed by 2 experts that found it of interest. However, there are many issues from the study design and many confounding factors needed to be, seriously, addressed before we can make a final decision about your submission.

Please, carefully, answer each and every criticism and make changes to the revised version.

We look forward to the revised manuscript.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeries

Artioli et al. reported data regarding the impact of the time-of-the-day on post-operative mortality and cardiovascular complications. Exploring a large cohort (>1200 patients), two subgroup were formed to categorized morning and afternoon surgeries. They observed higher rates of all-mortality at 1 month and 12 month in patient who underwent surgery in the afternoon.

The topic is of interest, because of the disparity in the results of these time-of-the-day post-operative complications studies. The discussion of the paper is well written and takes into account the major knowledge in the field.

However, the design of the study introduces some confounding factors, because the participant were not randomized.

We would suggest several points

if available data :

• Distribution with surgery schedule ? An histrogram of the distribution of surgery time-of-the-day should be provided.

• Divided Afternoon & night surgery � Recently Montaigne et al. published a paper regarding time-of-the-day and Kidney transplantation which should be discussed in line with the conclusion. It would be of interest to compare day-time and night surgery, by different medical organization ?

• Line 78 : The sentence is quite unclear. “it is poorly understood if daytime variation also occurs in the perioperative period”, please rephrase.

• Line 130 to 134 : In the paper of du Fay and collegues and Montaigne and collegues, an interval of 3 hours was observed between “morning” and “afternoon”.

• Line 154 : What is “considered clinically significant” ? High incidence of atrial fibrillation in the morning could distort the observations

• Line 202 : What type of vascular surgery ? Duration of the operation ?

• Table 1 : Please provide preoprative TnT and Left ventricular ejection fraction ?

• No exclusion criterias, why ? No flowchart ?

• Emergency surgery represent a high proportion of the afternoon group vs morning group and weights a lot in the Cox regression. Why this particular population is not excluded ? This is a major confounding factor that should be presented as a clear limitation.

• Fasting duration could be important in peri-operative studies, because of the amount of ketone bodies increasing in time. What was the fasting durations in each group (including emergency surgery) ? Was the ketonemia higher in any group ? This should be at least discussed. (Youm et al. Nat. Med. 2015)

• Is nosocomial infection an exclusion criteria from this cohort ?

• In this population (>1200 patients) case-control with propensity matching design would be of interest.

Reviewer #2: This is an interesting paper describing increased postoperative mortality both at hospital discharge and one year following vascular surgery in a tertiary centre for operations started after 12 mid-day compared to those whose operation was started in the morning between 7am and mid-day.

The paper illustrates well that those operated later in the day were sicker, higher cardiac risk and not surprisingly did less well immediately after surgery and even a year after (20.8% and 34.7% mortality !)

1. It is disappointing therefore that in the design of the study (and these results might well have been expected -what was the hypothesis?) data was not included at base line which might address the reason why operations started later in the day have sicker patients, more often are urgent/ emergent and do less well. Some factors are raised in the discussion but this study does not address the system issues.

2. The method describes that only Consecutive cases for whom a preoperative cardiological consultation was requested were included. There were 1267 patients but how many patients were there who didn’t have a cardiological consultation ? Obtaining this consultation may be affected by time of day or urgency ? Can the authors comment on this and preferably indicate how many other vascular surgical procedures were done without this consultation and what was the mortality rate for this group- to give a full picture of the context of this study.

3. In vascular surgical practice repeat operations are not uncommon how was this taken into account in the study.

4. No distinction is made regarding the nature of the vascular procedures done – it would be important to describe these as the outcomes, the open vs endovascular options, major vs minor and choice of time of day will be influence by these

5. Follow up was described both as 30 days and at -hospital discharge -which was it ? One year data was by telephone and registries. In the Survival data there are multiple steps – does this mean telephone calls were made regularly ?

6. The authors describe urgent/emergency surgery (how was this defined ? and how many of these underwent prior cardiological assessment? This was a very major difference in the two time groups 68% compared to 29.6% . The data suggests that this was the most important risk factor maybe even more so than time of day.

7. Most of the analysis is of patient characteristics and they were sicker but what of other system factors that would affect the time distribution? Was there any access to operating theatre issue – which pushed procedures in to the afternoon. Were there delays to surgery which pushed procedures to later in the day. Interestingly urgency was a major risk factor for MACE

8. The pattern of referral to this tertiary hospital was mentioned - as a possible system factor. Regional referral patterns for vascular surgery are well recognised, which may be related to availability of vascular surgery specialists and appropriate support services. If not in the data collected can the authors please comment on the factors in their hospital/region that influence what they have reported which could lead to outcome improvement.

9. Discussion page 12 line 271 it says “Additionally, our population were exclusive of patients undergoing arterial vascular surgery, which are patients at greater cardiac risk undergoing mostly high-risk operations. -could the authors please explain ? Do they mean Additionally, our population included only patients …. Or Additionally, our population were exclusively patients undergoing …..

10. The Graphical abstract fig 2 should be revisited as it misses the point of the study – This reviewer would suggest that the study is not primarily about “need for better postoperative outcomes control” (not sure what that means). The message is about operations done later in the day – How can we insure the high risk patients are better prepared and more often operated earlier in the day.

11. Similarly the Conclusion should be revisited – Vascular surgery patients operated later in the day are sicker, more urgent and have worse outcomes with double the mortality at 30m days and even out to one year. Steps are needed to improve outcomes which may include starting operations earlier.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-21-21807R1Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeriesPLOS ONE

Dear Dr. Caramelli,

Thank you for submitting your revised manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Your manuscript has been reassessed by the two reviewers from the previous round, whose reports can be found below. As you will see from the comments, the reviewers acknowledge that the manuscript has improved, but there remain significant concerns (outlined by reviewer 2) that the manuscript does not clearly communicate the contribution your study makes to the body of academic knowledge. Please ensure you respond to each point carefully in your response to reviewers document, and modify your manuscript accordingly.

Please submit your revised manuscript by Aug 22 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Joseph Donlan

Editorial Office

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The remarks were taken into account appropriately. The few points that could not be corrected, due to the internal functioning of their hospital, were justified.

Reviewer #2: 1.Thank you and Appreciation to the authors for the attention given to the reviewers suggestions. The statistical tools used are well defended. This reviewer still has concern that the authors do not use this data to say something new or give strength to ways of dealing with the problem. The conclusion after all is not new - we all know about this phenomena.

The following comments are suggestions towards achieving this

2.The benefit of this paper to influence practice – while authors argue they wanted to have a clinical / clinician focus it

Assumes this will lead to change – but we have known for a long time that urgent procedures occur more often in the later part of the day with sicker people , reduced supporting services etc . Can the authors contribute more critically? If cardiology work up is so important – shouldn’t that be made more available – line 100 and 110. If this is true why not explore this in the data

3.Along the same lines in the method it says “This is part of a prospective cohort registry including consecutive patients undergoing non-cardiac arterial vascular surgery between 2012 and 2018 at Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil, for whom a preoperative cardiologic consultation was requested”. What does this mean – when you have included urgent patients who didn’t get this consultation. Your addition line 99-100 makes this confusing. Perhaps you could rewrite the description of your cohort

4 Is it not of interest to know who missed out - as requested in the previous peer review who were these and what the role of your preoperative assessment achieved for those who did get it ? Otherwise there is little relevance of mentioning preoperative consultation to the outcome of the study .

5.Reference to reoperation in previous review assumed the patients and the index procedure were only counted once but rather that reoperation has other possible implications – when reoperation is the index case, and that subsequent reoperation would be an important factor in outcomes at 30 days and one year.

6. Line 328 Not sure what the addition (redline version) means “We may have missed patients” ? see the confusion in comment 3 above. Does this mean all the patients (including the urgents) had vascular surgeon’s request made for cardiology consultation (and not all got it) and then there were a few for whom the vascular team didn’t get around to it and they are not in the study population ?

7. This comes back to what is the relevance of the consultation why is cardiac consultation important. It seems to this reviewer that the authors have alluded to this in the last paragraph but unfortunately have not used the data they have to explore this e.g there presumably are at least 1000 subjects who were referred for the cardiology consultation -

Another example you present data of differences in cardiac drugs - surely a benefit of seeing a cardiologist which indicates urgent cases seem not to be protected as well etc

Another example might be :Cardiac risk Index – speak of risk – can we presume this data is more likely to be documented by cardiology consultation ? This reviewer suspects this is far more important than fasting time !

8. Thankyou for the additional table This is quite revealing – amputations left to the end of the day , maybe for the juniors, often very sick, AAAE mainly during the morning – good idea , LLR being done late in the day . This deserves comment

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-21-21807R2Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeriesPLOS ONE

Dear Dr. Caramelli,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise.

Please submit your revised manuscript by Nov 04 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: No

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The account of who did and who didnt get cardiology consultation is at best confusing. If a patient with a rupture AAA appeared at 11 pm was cardiology consultation available or not prior to surgery ? What happened to all the patients for whom the anaesthetist made decisions. Why could you not previously account for who did and who did not have consultation when you now say only those with consultation were included in the study ?

Please describe your consultation service that sees all patients within 24 hours - what hours of the day is the service not available . Why the insistence to describe this service and use it as your selection criteria and not want to explore its relevance?

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-21-21807R3Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeriesPLOS ONE

Dear Dr. Caramelli,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please revise. 

Please submit your revised manuscript by Dec 01 2022 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #3: (No Response)

Reviewer #4: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #3: Partly

Reviewer #4: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #3: Yes

Reviewer #4: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #3: Yes

Reviewer #4: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #3: Yes

Reviewer #4: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #3: A very major flaw with this study is that there is no analysis made of “afternoon” surgery (ie normal working hours) and out of hours (emergent) surgery. Out of hours surgery will always have poorer outcomes given the emergent nature of the work.

Reviewer #4: (No Response)

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Reviewer #3: Yes: Sandeep Bahia

Reviewer #4: No

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Impact of the period of the day on all-cause mortality and major cardiovascular complications after arterial vascular surgeries

PONE-D-21-21807R4

Dear Dr. Caramelli,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #4: Yes

Reviewer #5: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #4: Yes

Reviewer #5: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #4: Yes

Reviewer #5: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #4: Yes

Reviewer #5: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #4: (No Response)

Reviewer #5: Logic outcomes and useful for the general vascular surgeons. It describes a very important problem that faces us.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #4: No

Reviewer #5: Yes: Aram Baram

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